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| ORIGINAL ARTICLE |
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| Year : 2014 | Volume
: 2
| Issue : 4 | Page : 205-216 |
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Progressive macular hypomelanosis pathogenesis and treatment: a randomized clinical trial
Azza M Hassan1, Marwa A El-Badawi2, Fatma A Abd-Rabbou2, Mohamed M Gamei2, Khaled A Moustafa3, Azza H Almokadem4
1 Microbiology & Immunology Department, Faculty of Medicine, Tanta University, Egypt
2 Dermatology & Venereology Department, Faculty of Medicine, Tanta University, Egypt
3 Histology Department, Faculty of Medicine, Tanta University, Egypt
4 Dermatology Department, El-Dammam Hospital, Saudi Arabia
| Date of Web Publication | 5-Feb-2018 |
Correspondence Address:
Azza M Hassan
Microbiology & Immunology Department, Faculty of Medicine, Tanta University
Egypt
 Source of Support: None, Conflict of Interest: None  | 5 |
DOI: 10.1016/j.jmau.2014.09.001
Background: Progressive macular hypomelanosis (PMH) is a cosmetically disturbing skin disorder that is poorly understood with indefinite treatment. The aim of the present study was to clinically outline PMH and study its pathogenesis. Based upon the literature suggesting improvement of PMH with antibiotic therapy to decrease Propionibacterium acnes (P. acnes) colonization, different treatment modalities were tried to reach the best treatment option.
Patients and methods: This study included 12 newly diagnosed PMH selected patients who attended Tanta University Hospital outpatient clinic of Dermatology and Venereology from June 2009 to March 2010. Patient’s lesions were subjected to wood’s lamp and potassium hydroxide (KOH) examination as well as biopsies used in histological, immunohistochemical, bacteriological and electron microscopic examination. A randomized clinical trial with different treatment modalities was applied.
Results: The patient’s mean age was 25 ±10.8 with significant female predominance (P=0.0001). Reduction of epidermal melanosomes and tyrosine activity together with difference in distribution of S100 proteins in hypopigmented skin was demonstrated. Abnormal distribution of tonofilaments was noticed inside keratinocytes with increased apoptosis. P. acnes were detected in hair follicles of 83.3% hypopigmented lesions. Administration of local and systemic antimicrobial treatment with narrow band ultraviolet B (NBUVB) phototherapy for 3 months was the best treatment modalities.
Conclusion: The etiology of PMH is multifactorial where genetic predisposition, the presence of P. acnes and hormonal imbalance play the main role. Administration of local and systemic antimicrobial treatment with NBUVB phototherapy for 3 months is an effective treatment regimen for PMH.
Keywords: PMH, EM, KOH, Immunohistochemistry, NBUVB, P. acnes
How to cite this article:
Hassan AM, El-Badawi MA, Abd-Rabbou FA, Gamei MM, Moustafa KA, Almokadem AH. Progressive macular hypomelanosis pathogenesis and treatment: a randomized clinical trial. J Microsc Ultrastruct 2014;2:205-16 |
How to cite this URL:
Hassan AM, El-Badawi MA, Abd-Rabbou FA, Gamei MM, Moustafa KA, Almokadem AH. Progressive macular hypomelanosis pathogenesis and treatment: a randomized clinical trial. J Microsc Ultrastruct [serial online] 2014 [cited 2023 Mar 20];2:205-16. Available from: https://www.jmau.org/text.asp?2014/2/4/205/224754 |
| 1. Introduction | |  |
Progressive macular hypomelanosis (PMH), also known as idiopathic multiple large-macules or nummular and confluent hypomelanosis of the trunk [1], is poorly understood and often misdiagnosed cosmetically disturbing skin disorder [2],[3]. It occurs all over the world in young adults of all races and is characterized by symmetrically distributed ill-defined nummular, non-scaly, hypopigmented macules mainly on the trunk. Inflammatory predisposition is absent and the lesions tend to progressively increase in number, sometimes extending to the neck, face, buttocks and upper half of extremities [4],[5]. These lesions appear to be less densely pigmented with less mature melanosomes than normal skin as indicated by histological and electron microscopic (EM) examination [6]. Up till now the course and prognosis as well as specific treatment to PMH is not well known [4].
Many theories have been proposed to clarify its pathogenesis, however, hard facts in support of these ideas are lacking [4]. Melting of genes between white and black parents in patients of mixed racial background was speculated by Guillet et al. [2]. Switching between type IV singly aggregated melanosomes to type I—III aggregated melanosomes in the hypopigmented skin lesions of PMH provided an evidence for such theory [7]. Because he noticed the disorder only in family members, Borelli [8] suggested that PMH is a genodermatosis. According to Lesuer et al. [9], PMH might be related to tinea versicolor although its causative organism, the yeast Malassezia furfur, was never detected. In a case study report, Lo Schiavo et al. [10] pointed to the possible role of antiretroviral drugs in the pathogenesis of PMH as they noticed that receiving post HIV prophylaxis was the only risk factor reported.
Westerhof et al. [4] was the first to offer Propionibacterium acnes  > impact based on its presence in high density in their lesional skin pilosebaceous units and the observed red fluorescence inside the hypopigmented spots by ultraviolet (UV) radiation. However, the mechanism by which P. acnes may induce PMH is uncertain, although several hypotheses were proposed. First, the production of bacterial enzymes with degradative properties that target the integrity of epidermal skin cells and the barrier function of sebaceous follicles [11]. Second, P. acnes might be involved in triggering inflammation by constitutively produced factors such as porphyrins, surface determinants like a glycocalyx polymer or stress proteins, an acid shift, or heat shock [11],[12]. Last, P. acnes contain genes encode CAMP factor homologs that act as pore-forming toxins [13],[14], which may affect the function of melanocyte [4]. In contrary, Relyveld et al. [15] hypothesize that the species causing PMH differ from that causing acne, and cannot be differentiated by conventional culture and biochemical methods.
The aim of the present study was to clinically outline PMH, study its histological and immunohistochemical pictures and determine its bacteriological aspect to throw a light on its pathogenesis. Based upon the literature suggesting improvement of PMH with antibiotic therapy to decrease P. acnes colonization [16], different treatment modalities are tried to reach the best treatment option.
| 2. Patients and methods | | |
2.1. Patients
This study included 12 newly diagnosed PMH selected patients who attended Tanta University Hospital outpatient clinic of Dermatology and Venereology in the period from June 2009 to March 2010. The disease was discussed with the patients who signed an informed written consent.
2.1.1. Inclusion criteria
The chosen enrolled patients were selected according to the following criteria: (a) clinically diagnosed cases of acquired, non scaly, confluent, hypopigmented macules and patches with normal sensation, (b) wood’s light examination for accentuation of the clinically diagnosed lesions and diagnosis of subclinically undiagnosed one, (c) exclusion of fungal infection by KOH examination, and (d) histopathologically proven from biopsies taken from lesion and adjacent normal skin [2],[7],[16].
2.1.2. Exclusion criteria
Patients were excluded if they had hypopigmentation due to other diseases, they were under medical treatment or phototherapy for the disease or they refused skin biopsy.
2.1.3. Controls
Control samples were taken from the apparently normal nearby skin of the selected cases.
2.2. Methods
After complete history taking and thorough general and cutaneous examination, patient’s lesions were subjected to wood’s lamp and KOH examination to confirm the diagnosis and exclude fungal infections. Skin of the selected patients was disinfected and two punch biopsies (4 mm each) were taken from each patient, one from the hypopigmented and the other from the normal nearby skin. Specimens were divided into many parts for histological, immunohistochemical, bacteriological and EM examination.
2.2.1. Wood’s lamp examination
Wood’s lamp (Waldmann WTM) examination was done according to Gilchrest et al. [17], with the following precautions: (a) patient’s skin was examined from a distance of 5–20 in. after cleaning with alcohol in perfectly dark room, and (b) common sources of error as bluish or purplish fluorescence produced by ointments on the skin-containing petrolatum, green fluorescence by salicylic acid containing medicaments on the skin and light reflected from the examiner’s white coat producing a light blue fluorescence were avoided.
2.2.2. KOH examination
After cleaning the skin with alcohol, scraping of the hypopigmented skin on a clean sterile glass slide was done, followed by adding a drop of 15% KOH, then mixing. A cover glass was put over the preparation and was allowed to remain at room temperature until the material has been cleared which may be warmed to speed the clearing process. Slides were examined by light microscope at X10, and X40 power [18].
2.2.3. Histological examination
Specimens were fixed in 10% buffered formalin, processed, and embedded in paraffin then subjected to:
2.2.3.1. Haematoxylin and eosin stain. Sections (5 mm thick) were prepared for hematoxylin and eosin (H&E) from tissue embedded paraffin blocks. Melanin pigment colored brown [19].
2.2.3.2. Fontana-Masson silver stain. Sections were deparaffinized in xylene, hydrated in a graded series of alcohol and treated with silver solution (ammonia in 20 ml of 10% silver nitrates then 20 ml of distilled water) at room temperature over night in the dark. After washing, sections were treated with 5% sodium thiosulphate for 2 min, washed, dehydrated and mounted in Canada balsam. Melanin pigment appeared black [20].
2.2.3.3. DOPA-oxidase reaction. This method was carried out according to Praver and Tatcher [21]. Briefly, sections were placed in 0.1% DOPA in 0.1 phosphate buffer (pH 7.4) at 37 °C for 1 h followed by immersion in another fresh DOPA reagent for 12 h at room temperature. After washing, fixation in Bouin’s solution was done for 24 h. Slides were then dehydrated, cleared with xylene, and embedded in wax. Sections of 4 μm thickness were put on glass slides, washed and H&E was used as a counter stain. On microscopic examination, brown granules of melanin appeared at the sites of DOPA-oxidase activity.
2.2.4. Immunohistochemical staining
This staining was performed to detect the presence of melanocytes in hypopigmented skin in comparison with the nearby normal looking skin. All reagents except the primary antibody were “universal kit”. Sections of 4 μm were cut from formalin fixed paraffin embedded blocks on positive charged slides (Superfrost plus-Biogenix), deparaffinized and rehydrated. Blocking of the endogenous peroxidase was done by 3% hydrogen peroxide and antigen retrieval was done by 10 ml mol/L citrate buffer (pH 6.0). Blocking reagent (normal mouse serum) was added followed by S100 primary antibody (S-100 protein ab-1, clone 4C4.9 ready to use for immunohistochemical stain) with an over night incubation. The secondary biotinylated antibody was placed on each slide before exposure to streptavidin enzyme label then color reagent and finally, Mayer’s hematoxylin counterstain. Sections were dehydrated in alcohol and mounted in DPX. Section of normal skin was used as positive control tissue for S100. Positive staining was indicated by the presence of brown color [22].
2.2.5. Bacteriological examination
2.2.5.1. Bacterial culture. First, surface swabs were taken from normal and hypopigmented skin and cultured according to the standard technique [23]. Then, parts of the biopsy from normal-looking and hypopigmented skin were cultured after preparation by modification of Westerhof et al. [4] method. Biopsies were ground with few drops of broth in a sterile mill and tissues were immediately swabbed on blood agar plates. One half was cultured under aerobic conditions (5% carbon dioxide at 37° C), and the other half was cultured under anaerobic conditions into an anaerobic jar (80% nitrogen/10% hydrogen/10% carbon dioxide) for 48 h at 37° C. Colonies were identified by their morphology and Gram staining characters.
2.2.5.2. Gram stain. Gram stain was done for bacterial smear from ground tissue and bacterial cultures as well as from unstained serial sections from the paraffin block [24].
2.2.6. Electron microscopic examination
2.2.6.1. Electron microscope. Skin tissue specimen, 1–2 mm3 in size, was fixed as soon as possible in 4% paraformaldehyde for two hours at 4°C, washed by buffer three times for ten minutes each at 4 °C, post-fixed in 1% phosphate buffered osmium tetroxide for 30 min and washed by buffer three times for 10 min each at 4°C. Dehydration was done in ascending grades of ethanol at 4 °C. Specimens were transferred into pure propylene oxide followed by propylene epoxy resin mixture then pure epoxy resin. Embedding was done in labeled capsule filled at about 2/3 of their volumes with fresh epoxy resin mixture to which the accelerator dmp-30 was added as 1% by volume.
After polymerization in an oven for five days, sectioning was performed where 0.5–1 μm semi-thin sections were used to select suitable areas for ultrathin sectioning for the electron microscopy. Ultrathin sections of either gray or silver color were picked upon 200 mesh naked copper grids. The grid with sections were dried then placed in a dust free grid box. Grids were stained by lead and uranium double stained procedures, stored in grid box to be examined and photographed [25].
2.2.6.2. EM-DOPA reaction test. Small skin samples were fixed with 2% glutaraldehyde and incubated in 0.1% DOPA/phosphate buffer for 5 h at 37°C, then post-fixed in 1% osmium tetroxide for 2 h. After dehydration, the specimens were embedded in Epon. Ultrathin sections were cut and examined by transmission electron microscopy [26].
2.3. Therapeutic trials
In this work, a randomized clinical trial of various therapeutic modalities with different therapeutic lines were performed using local erythromycin 2% lotion twice daily, systemic doxycycline HCl 100 mg twice daily, and narrow band ultraviolet B (NBUVB) with Cosmedico™ apparatus. In NBUVB clinical trial, the initial dose was variable according to the skin type and gradual until reaching the minimal erythema dose. The sessions were done twice weekly for periods ranging from 12 to 24 sessions with or without stimulation of melanogenesis. Of notice, two patients refused to receive medical treatment to detect the course of the disease.
Several modalities were tried: (1) Local and systemic antibacterial treatment accompanied by NBUVB (2 patients for three months), (2) Local and systemic antimicrobial treatment for one month followed by NBUVB for 2 months. Patients were instructed to continue the local treatment for two months with the same dose, but systemic treatment once daily for one month only (3 patients), (3) Local and systemic treatment without NBUVB (2 patients), (4) Local treatment accompanied by NBUVB for three months (one patient), (5) Local treatment only for three months (one patient), and (6) NBUVB only for three months (one patient).
Randomization was done by closed envelope method. Assessment of the results were obtained according to three dermatologic points of view who were blinded for the assigned treatment modality plus the patient opinion and scoring photographs before and after treatment during the three months of treatment and over a follow up period of about six months. Scoring of the results was fair: < 25%, good: 25-50%, very good: > 50–75% and excellent: >75% according to the number of repigmented lesions.
2.4. Statistical analysis
It was performed by using SPSS for Windows, version 9. Data were expressed as range and mean ± standard deviation (SD)/median or numbers and percentages. Pearson Correlation Coefficient was used to detect the relation between variants. Univariate analysis was done by Fisher’s exact test. For all statistical tests done, P value < 0.05 was considered significant.
| 3. Results | | |
This study included 12 patients with PMH selected from outpatient clinic of Tanta University Hospitals. Their ages ranged from 7 to 52 years (mean ±SD: 25 ±10.8). There was female predominance (67% females vs. 33% males, P = 0.0001). Two patients were skin type III and 10 patients were skin type IV according to Fitzpatrick classification of skin type [27] [Table 1]. | Table 1: Demographic and clinical characteristics of the studied patients.
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3.1. Clinical results
The duration of the lesions in the studied cases ranged from 6 months to 20 years. Pearson Correlation Coefficient has revealed that both age and the duration of the disease were negatively correlated with the size of macules (−0.31 and −0.41, respectively) [Figure 1]. All patients were Egyptian patients of unmixed ethnicities who had no history of recreational sun exposure. Regarding previous treatment, 8 patients used previous topical and systemic antifungal drugs with no effect, one patient was diagnosed as post eruptive hypopigmentation, and another one had many previous diagnoses such as vitiligo, post eruptive hypopigmentation and pityriasis alba. Only two patients were asking medical advice for the first time. Interestingly, two of the patients were twins while the rest of the patients gave no family history. [Table 1] No history of consanguinity was obtained in all patients. In one patient lesions extended on the buttock while in another patient lesions were also present on the breast and neck and 50% of patients had acne lesions on the face. | Figure 1: Linear regression correlation. It reveals negative correlation between age (A) and duration (B) of the disease and size of the macules. Pearson correlation coefficient = −0.31 and −0.41, respectively.
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3.2. Histological results
Histological examination with H&E stain had excluded all other diseases that could be differentiated from PMH. It also revealed decreased melanization in the epidermis compared with the adjacent healthy skin with no abnormalities in the dermis. In the lesional skin of 7 (58.3%) patients, there was a mild perifolliculitis with bacteria residing inside the hair follicle. In the stratum corneum, no spores, hyphae, or bacteria were seen [Photo 1]. By Fontana-Masson stain, the melanin content was evaluated. All hypopigmented lesions showed decrease melanin granules concentration as compared with normal skin (20%–30% vs. 50%–72%, P =0.012). [Photo 2]; [Figure 2] Dopaoxidase reaction was performed to evaluate the activity of tyrosinase enzyme. A decreased in this reaction was notice in hypopigmented skin than normal skin [Photo 3].
 | Figure 2: Percentages of melanin granules concentration in normal and lesional skin.
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3.3. Immunohistochemical results
There was apparently no difference in the number of S-100 protein-positive cells between the hypopigmented and normal-appearing skin. However, on high power magnification there was difference in distribution of these proteins where in normal skin it was mainly supranuclear, but in hypopigmented skin it is dispersed all over the cell [Photo 4] and [Photo 5].
3.4. Bacteriological results
3.4.1. Gram stain
Grams positive, non-sporing bacilli of P. acnes were seen in hypopigmented skin (7 patients, 58.3%, P= 0.0046) and absent in normal skin. They were detected in both serial sections from unstained paraffin block [Photo 6]a and in bacterial smear from ground skin biopsy [Photo 6]b and from bacterial culture.
3.4.2. Bacterial culture
Anaerobic cultures were positive for P. acnes in hypopigmented skin and negative in normal skin. The bacilli were detected by modification of Westerhof et al. method [1] not in surface swabs. Bacterial growth was identified by morphologic colony type, which showed arborizing growth pattern and the violet rod-like structure of the gram staining.
3.5. Electron microscope results
3.5.1. Ultrastructural results
Lesional skin contains significantly more immature melanosomes [Photo 7]a, while normal skin contain more mature melanosomes [Photo 7]b with a P value less than 0.0001. Normal skin type III showed significant predominance of stage three mature melanosomes, while normal skin type IV showed significant predominance of stage four mature melanosomes (P<0.0001). [Figure 3] In normal skin melanosomes are mainly supranuclear [Photo 7]b and [Photo 8]a, while in the hypopigmented skin melanosomes are dispersed all around the nucleus and are surrounded by a band of tonofilaments, which form a mesh entrapping them [Photo 7]a. Increased keratinocyte apoptosis in hypopigmented [Photo 8]b and [Photo 8]c than in normal-looking skin [Photo 8]d.
 | Figure 3: Comparison of melanosome maturation between normal and lesional skin. Immature melanosomes were significantly detected in lesional skin compared to normal skin (P < 0.0001).
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3.6. Response to different therapeutic modalities
Two patients had refused treatment and excluded from this clinical trial. Treatment with local and systemic antimicrobial agent in addition to NBUVB gave the best outcome with complete cure in both cases after 3 months of therapy and without any signs of relapse during the follow up period [Photo 9]. Nearly similar profile but with slightly lower sensitivity was notice in the patient who received local antimicrobial therapy with NBUVB (92%) for 3 months, that who exposed to NBUVB (90%) only for 3 months and those who had local and systemic antimicrobial agents for one month followed by NBUVB (90%). However, treatment with local and systemic antimicrobial agents for one month followed by NBUVB gave complete cure in about 5 months in one case, while use of NBUVB was the only modality that showed relapse after one month. Of notice, the lowest response was detected in the 3rd and 5th modalities where NBUVB was not applied (73% and 74%) [Table 2].
 | Table 2: Outcome of active treatment using different modalities (3 months) and at the end of follow-up period (6 months).
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| 4. Discussion | | |
Progressive macular hypomelanosis is a poorly understood skin disorder characterized by hypopigmented macules without scales, history of skin problems or effective treatment [5]. To the best of our knowledge, until the present date PMH has not been fully reported in Africa or Middle East. The present study aimed to describe PMH on the basis of clinical, histological, immunohistochemical, microbiological, and ultrastructural study in a trial to gain an insight into its pathogenesis and therefore the best treatment modality.
In the present work the mean age of onset was 25 years with significant female predominance. Several authors have observed PMH only in adolescents and young adults [2],[4],[27],[28]. However our observation of PMH in a young child may open a wide range for PMH incidence. On the other hand, the female predominance may be related to the fact that women are known to seek medical advice more for cosmetic reasons, especially at the age of marriage, hormonal imbalance, and/or the random choice of patients. Neynaber et al. [5] noticed progression of hypopigmentation during pregnancy. Guillet et al. [7] and Westerhof et al. [4] observed PMH mainly in women, but Borelli [8], mentioned an equal distribution in both sexes. Other studies pointed to male predominance in PMH [29],[30],[31]. Hwang et al. [28] concluded that the exact prevalence of PMH is unknown. It is worth to be noted that several patients were diagnosed clinically with typical PMH symptoms, but were excluded from their study because of their refusal of skin biopsy, which support the under-reporting of PMH cases. Acne vulgaris on the face was detected in half of patients, however, consistent with other studies [4],[15], acne does not seem to predispose for PMH in this study.
Clinically, the majority of patients were skin type IV that may be due to the fact that white spots are more easily recognized on pigmented skin [4]. Regarding the course of the disease, spontaneous regression of PMH was not detected from history or over the follow up period in spit of the negative correlation detected between both age and duration of the disease with the size of the macules. However, the term progressive is misnomer because after hypopigmentation reaches certain limit in every patient, it becomes stationary. There are many follow-up reports of PMH. Guillet et al. [2] suggested that hypopigmented lesions spontaneously decrease after 2–5 years. Hwang et al. [28] followed 3 patients who did not receive treatment for 3 months. Only one of those patients improved, with a time-to-repigmentation of 8 years. They concluded that more extensive follow-up is needed to confirm the spontaneous resolution of PMH. Symmetrical distribution of the macules is documented [2],[3],[5],[6]. Recently, Wen et al. [32] reported their first PMH case with asymmetrically distributed lesions, which suggesting the existence of some other subtypes of PMH.
Although this study showed the presence of mature melanocytes in hypopigmented lesions with no apparent difference in the number of S-100 protein-positive cells between the hypopigmented and normal skin, reduction of epidermal melanization of melanosomes, melanin granules concentration together with difference in distribution of S100 proteins in hypopigmented than normal skin, which was more manifest in Fitzpatrick skin type IV than type III, was demonstrated. Additionally, abnormal distribution of tonofilaments was also noticed inside keratinocytes with presence of disintegrated melanosomes in the lysosomal compartments and increased apoptosis. These observations pointed to that the disease is not caused by abnormalities in melanocytes and PMH is hypomelanotic not hypomelanocytic, which may be due to the abnormal distribution of tonofilaments resulting in changing of the maturation, size, number and distribution of melanosomes in lesional skin [33]. On the contrary, Relyveld et al. [27] found no defects in melanosome degradation and they concluded that a decrease in melanin synthesis must be the explanation for hypopigmentation in PMH.
In a trial to go in depth of the pathogenesis of hypomelanosis noticed and proved by EM suggesting that there is probably a functional defect in pigmentation or a problem in melanin distribution, further ultrastructural examination was done using EM-DOPA technique to demonstrate the status of tyrosinase activity for the first time in PMH. After incubation with DOPA solution nearly all melanosomes changed to stage four mature melanosomes in normal skin, while only some immature melanosomes changed to mature stage three and four melanosomes in hypopigmented skin with detection of stages one and two melanosomes and indicating a reduced tyrosinase activity.
In this study, bacterial examination was done to detect P. acnes, which were incriminated by Westerhof et al. [4] to be the causative factor of PMH. They added that the mechanism they propose is not new in the biology of pigmentary disorder. In 1986, Nazzaro-Porro et al. [34] suggested that the hypopigmentation in PV is probably due to toxic lipoperoxidases formed by the action of Pityrosporum ovale on the unsaturated lipids of the skin surface. However, the mechanism by which P. acnes trigger PMH is not certain, but stress, production of degradative enzymes, provoking of inflammation or production of pore-forming toxin are attractive theories [11],[12],[13],[14].
Gram-positive bacteria were found in the serial sections of the pilosebaceous ducts of hypopigmented skin and were absent in normal skin, and P. acnes have been cultured from follicular lesional skin from patients with PMH. It is worth to be noted that surface swabs cannot detect P. acnes as it lies deep in the hair follicle [4]. Red follicular fluorescence was not observed in this study which may be due to that a density of 1000 P. acne organisms were required for follicular fluorescence to occur as was explained by McGinley et al. [35].
We have tried different therapeutic modalities in a clinical trial to test a treatment regimen that is directed against the P. acnes with or without stimulation of melanogenesis. It was noticed that NBUVB combined with topical and systemic antimicrobial gave the most excellent response with complete cure. On the other hand, the use of antimicrobial agents alone and relapse after one month stoppage of NBUVB alone suggests that P. acnes have a role in the pathogenesis of the disease while NBUVB has a role in acceleration of cure.
Several studies have tried several therapeutic modalities to treat PMH as topical and systemic antifungal agents, topical steroids, topical antimicrobial agents, and phototherapy, however, no consistently effective therapy has been established [16],[28],[36],[37],[38]. Relyveld et al. [16] compared the effectiveness of antimicrobial lotions with anti-inflammatory cream in patients with PMH. They concluded that antimicrobial therapy with UVA was a more effective treatment modality, which supports the hypothesis of Westerhof et al. [4] that PMH is causally related to P. acnes. Similar result was obtained by Wu et al. [39] and supported by Cavalcanti et al. [40] who treated a series of thirteen PMH patients with an association of antiacne lymecycline and benzoyl peroxide over a three-month period. Response to treatment was excellent and the positive results were maintained during the entire follow up period. Later on, Kim et al. [41] showed similar excellent response to oral isotretinoin which is used for treatment of sever acne.
Regarding phototherapy, Choi and Hann [42] have observed disappearance of the hypopigmented spots with psoralen plus UVA (PUVA) therapy but after cessation of this treatment, the induced pigmentation disappeared immediately and resulted in a pattern of hypopigmentation exactly as before. This phenomenon is possibly the result of temporary inhibition of P. acnes by PUVA therapy while stimulating melanogenesis. Of notice, Chung et al. [36] reported that his patient improved after NBUVB phototherapy. Hwang et al. [28] noticed that six patients treated with NBUVB phototherapy showed marked repigmentation and hypopigmented lesions did not recur during 3–13 months of follow-up suggesting that NBUVB phototherapy is an effective treatment. Such results were supported by Kim et al. [43]. NBUVB phototherapy was shown to promote melanocyte proliferation and migration and to diminish the activation of interleukin-6 and tumor necrosis factor-α, which suppress melanin synthesis [44]. On the contrary, in the comparative study of Duarte et al. [45] no significant difference was found between the outcomes obtained with PUVA and those obtained with narrowband UVB phototherapy and they concluded that they did not prevent recurrence of the disease.
In conclusion, the present study suggested that the etiology of PMH is multifactorial where genetic predisposition may play a role for the reason that two of our patients were twins and the occurrence of PMH in a young child, together with the presence of P. acnes which may suppress the tyrosinase enzyme and affect melanosome transfer inside keratinocytes and hormonal imbalance as most of patients included in this study were young females had the main role. Additionally, administration of local and systemic antimicrobial treatment with NBUVB phototherapy for 3 months was the best treatment modality in PMH.
Conflicts of interest
The authors declare that there is no conflict of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]
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